Behavior of pyrene as a polarity probe in palmitoylsphingomyelin and palmitoylsphingomyelin/cholesterol bilayers: A molecular dynamics simulation study

Abstract

Pyrene is a polycyclic aromatic hydrocarbon noted for its remarkable optical spectroscopic properties. Among its uses as a fluorescent probe, measurement of lipid bilayer's equivalent polarity through the pyrene Ham effect stands out. To this effect, the ratio of the intensities of the first and third vibronic bands (I 1 /I 3 ) in its emission spectrum of pyrene is measured. However, issues concerning the precise location of bilayer-inserted pyrene and the possibility of probe-induced perturbation of host bilayer properties are potential sources of concern in this regard. Atomistic molecular dynamics simulations constitute a useful method for the characterization of lipid membrane systems, and, in particular, to understand the behavior of fluorescence probes upon incorporation in lipid bilayers. In this report, we present a detailed characterization of the behavior of pyrene in fluid Npalmitoylsphingomyelin (PSM) and PSM/cholesterol membranes, with emphasis on the degree of proximity between the probe and water molecules inside bilayers, related to the use of pyrene to measure equivalent lipid bilayer polarity. It is concluded that pyrene exerts minor effects on bilayer properties, with slight local disordering being apparent for high cholesterol content. Whereas rotation and lateral diffusion of pyrene are greatly slowed in cholesterol-rich systems, its relative transverse location is not significantly affected. While hydration of PSM bilayers, as sensed by pyrene, is already low compared to that of fluid phosphatidylcholine, it becomes even smaller for high cholesterol mole fraction at the studied temperature.

Interaction of NBD-labelled fatty amines with liquid-ordered membranes: a combined molecular dynamics simulation and fluorescence spectroscopy study

“…Order parameter profiles calculated for both chains of POPC and SpM (Fig. S5 in the ESI †) agreed well with both experimental and simulated data for POPC/Chol, 60,71,82 as well as for SpM/Chol 71,75,83 bilayers. Incorporation of NBD-C n does not induce any significant perturbation in the bilayer.…”

“…71 Specifically, the average area per SpM agrees with that obtained for the same composition and area partition method, using a different force field of A PL = (0.509 AE 0.012) nm 2 . 75 Bilayer thickness and position of different atoms and SpM/Chol bilayers. In general, the positions of the atoms of the NBD-fatty amines are consistent with the perpendicular orientation relative to the bilayer plane, with the NBD group near the head group/glycerol backbone region and the methyl group at the end of the fatty-chain, Cter, directed to the centre of the bilayer.…”

Influence of the sterol aliphatic side chain on membrane properties: a molecular dynamics study

“…40,41 The UA structure and topology of cholesterol were adapted from that of Ho ¨ltje et al 42 (available for download at the GROMACS webpage 43 ) by changing the molecule types from CH2/CH3 to LP2/LP3 to avoid overcondensation of the bilayer, as previously suggested, 44,45 and successfully tested by us. 46 Parameterizations of the other sterols were adapted from that of cholesterol by removing/adding the appropriate number of methylene groups from/to each chain, for androstenol and i-C5, or the other sterols, respectively. Water was modeled with the simple point charge model.…”

Diphenylhexatriene membrane probes DPH and TMA-DPH: A comparative molecular dynamics simulation study

“…This can be quantified by the average water density sensed by the fluorophore b ρ(water)N fluorophore (taken as the whole molecule for DPH, and atoms 1-16 in Fig. 1 for TMA-DPH), calculated according to [81] ρ Another noticeable difference between the density profiles of DPH and TMA-DPH across the bilayers is the higher probability of finding the former near the bilayer center (z = 0). This observation led us to investigate the possibility of probe translocation between the bilayer leaflets.…”